The site-selective delivery of cytotoxic agents, radionuclides, toxins or pro-flammatory substances to tumors by conjugation of these agents to monoclonal antibodies specific for tumor-associated antigens offers the promise of important advances in cancer diagnosis and therapy. At present the use of human antibodies is limited and therapeutic and diagnostic applications are not practical. Therefore, it is necessary to resort to antibodies derived from appropriate animals--usually the mouse. Since these antibodies are foreign to the human, an immune response is to be expected and indeed is often noted as discussed by J. W. Larrick and J. M. Bourla in Prospects for the Therapeutic Use of Human Monoclonal Antibodies, J. Biol. Responses Modifiers, 5, 379-393 (1986).
Moreover, antibodies may be formed in response to foreign proteins (e.g. toxins) coupled to the therapeutic antibody. Even with human or chimeric (human constant plus mouse variable regions) antibodies an immune response is a possibility. This response involves the formation by the host's B-lymphocytes of antibodies to the administered antibodies or other foreign proteins as discussed by R. C. Kennedy et al in Scientific American, 225, 48 (1986). When they occur, such responses compromise the therapeutic approach since they neutralize the therapeutic antibody before it has had the opportunity to carry out its function. In addition, there is also the possibility of serious hypersensitivity reactions which may endanger the patient as discussed by L. Chatenoud in The Immune Response Against Therapeutic Antibodies, Immunology Today, 7, 367-368 (1986) and M. L. Zoler in Monoclonal Antibodies: On the Verge of Therapeutic Reality? Medical World News, 92-108, June 9, 1986. In order to minimize the immune response, a mammal can be treated with a variety of known immunosuppressive agents, alone or in combination, such as corticosteroids, cyclosporin, cyclophosphamide and others. These agents, although partially effective, are non-selective and generally suppress many components of the immune system and consequently to obtain the desired suppression of the mammal's humoral response, serious and even life-threatening side-effects can occur as a result of the concomitant action against other immune system components. This invention provides a novel, specific and therefore more preferable procedure to temporarily suppress that component, and only that component, of the immune system which is responsible for the antibody response to foreign proteins, such as murine-derived antibodies, namely the B-lymphocytes.